1. Field of the Invention
This invention relates to novel compounds which are useful for enhancing the learning capacity of mammals, including man, and they have been found to have a profound beneficial effect in human geriatric patients by increasing their mental alertness and improving their mental attitude and physical appearance without the undesirable stimulant side effects commonly associated with amphetamines.
In another aspect, this invention relates to a method of preparing the novel compounds. In still another aspect, this invention relates to a method of enhancing the learning capacity of mammals. In a further aspect, this invention relates to compositions useful in the method of enhancing the learning capacity of mammals.
2. Description of the Prior Art
Numerous compounds structurally related to amphetamine (.alpha.-methylphenethylamine) have been prepared and reported in the literature and are the subject matter of various patents. Of particular interest with respect to the compounds disclosed herein are U.S. Pat. No. 3,547,999, Shulgin, A. T.: Chemistry and Structure-Activity Relationships of the Psychotomimetics which appeared in the book, Psychotomimetic Drugs, Ed. D. H. Efron, Raven Press 1970 and Shulgin, A. T., Sargent, T. and Naranjo, C.: Structure-Activity Relationships of One-Ring Psychotomimetics, Nature, 521-537 (1969). The foregoing patent and references disclose compounds closely related to the compounds of this invention. However, none of the compounds is disclosed as having the activity of the compounds of this invention. The Shulgin article in Psychotomimetic Drugs at pages 35-36 indicates that a "four chain compound" had been synthesized; however, the particular compound synthesized is not named, the structure is not disclosed, the method of preparation is not disclosed and no utility is disclosed in the article.
(3) Other patents and publications reported from a search are U.S. Pat. No. 2,246,529; Journal of the American Chemical Society, Vol. 78, pages 4419-22 (1956); Journal of Medicinal Chemistry, Vol. 9, No. 4, pages 469-70 (1966); Arch. int. Pharmacodyn Vol. 154; No. 1, pages 26, 31-32 (1965); Chemical Abstracts, Vol. 61, page 6954a; Chemical Abstracts, Vol. 71, page 12786q; Chemical Abstracts, Vol. 67, pages 10215w; Chemical Abstracts, Vol. 72, page 12364w; and Chemical Abstracts, Vol. 59, page 3797d.
Belgian Pat. No. 806,990 describes and claims the compounds having the formula ##STR3## wherein R.sup.1, R.sup.2 and R.sup.3 are alike or different and each is (lower)alkyl. The patent describes a method of preparation that is non-stereospecific.
D. E. Nichols, C. F. Barfkneckt and D. B. Rusterholz describe the "Asymmetric Synthesis of Psychotomimetic Phenylisopropylamines" in the Journal of Medicinal Chemistry, 1973, Vol. 16, No. 5, 480-483.
C. F. Barfknecht and D. E. Nichols, in J. Medicinal Chemistry, 14, 370-2 (1971), disclose inter alia the compound of the formula ##STR4## which is the lower homolog of one of the compounds claimed herein. However, unlike the compounds of the present invention, that compound was disclosed as having mescaline-like side-effects which are much more profound than those produced by DOM.
Chemical Abstracts, 81, 104988s (1974) (corresponding to West German OLS No. 2,355,350) discloses the compound of the formula ##STR5## as the racemate and the optically active antipodes. The compound improved the chronic avoidance aquisition of rats.
U.S. Pat. No. 3,457,354 discloses compounds of the formula ##STR6## in which X is --OH or --NH.sub.2 and R is H, --CH.sub.3 or --C.sub.2 H.sub.5 as antihypertensive agents.
U.S. Pat. No. 3,655,737 discloses compounds of the formula ##STR7## in which R.sup.1 is --CH.sub.3, --C.sub.2 H.sub.5 or --C.sub.3 H.sub.7 and R.sup.2 (in position 2, 4, 5 or 6) is F, Cl, Br, --CH.sub.3, --C.sub.2 H.sub.5 or --C.sub.3 H.sub.7 as antihypertensive and antidepressant agents.
A. T. Shulgin, in Experientia, 19, 127-8 (1963), reports the testing of a series of mescaline homologs of the formula ##STR8## in which R varied from H through C.sub.7 H.sub.15. He reports that toxicity and behavioral studies with mice could not distinguish between the first three members of this series (i.e. the ethylamino, propylamino and butylamino compounds). In humans it is established that the compound in which R is CH.sub.3 (the propylamino compound) is more than twice as potent as mescaline (R = H; the ethylamino compound), but Shulgin found that the compound in which R = C.sub.2 H.sub.5 (the butylamino compound) produced neither central nervous system activity nor psychtotomimetic (hallucinogenic) disturbance. Surprisingly, the compounds of the present invention have been found to possess the desirable central nervous system activity (e.g. enhancement of learning capacity and improvement of mental alertness) without the undesirable psychotomimetic side-effects.